1. Field of the Invention
The present invention relates to the treatment of radiation- and/or chemotherapy-induced injuries. More particularly, the present invention relates to a method and pharmaceutical composition for increasing therapeutic gain in radiotherapy and chemotherapy.
2. Description of the Related Art
Radiotherapy with or without concurrent or sequential chemotherapy is an effective modality for head and neck, breast, skin, anogenital cancers, and certain nonmalignant diseases such as keloid, desmoid tumor, hemangioma, arteriovenous malformation, and histocytosis X. However, the therapeutic benefit is limited by radiation- and chemotherapy-induced mucosal epithelium injuries and cutaneous radiation syndrome (CRS), which include acute reactions of tissue swelling, mucositis, dermatitis, desquamation, and ulceration, and long-term effects of tissue/skin fibrosis, necrosis, and the development of life-threatening sequelae of sarcoma, squamous and basal cell carcinoma (Peter, R. U. The cutaneous radiation syndrome. Advances in the treatment of radiation injuries, pp. 237-240. Oxford: Elsevier, 1996). In fact, the skin is affected in every form of the external radiotherapy of internal organs, and mucositis can occur in the oral cavity, esophagus, gastrointestinal tract, bladder, vagina, rectum, lung, nasal cavity, ear and orbita as a side effect of chemotherapy and radiotherapy. The application of steroidal or nonsteroidal anti-inflammatories is the most common treatment for radiation and chemotherapy-induced tissue injury, yet the results are unsatisfactory. An approach to selectively reduce skin morbidity without compromising the tumor-killing effects of radiotherapy and chemotherapy is a long-sought goal in radiation and medical oncology.
Drugs that have previously been tested in the management of radiation- and chemotherapy-induced damage include antioxidants (vitamin E and superoxide dismutase), anti-inflammatory agents (corticosteroids, colchicines, D-penicillamine, and TNF-α antagonist antibodies), and anti-fibrogenic agents (interferon, TGF-β antagonist, and angiotensin-converting enzyme inhibitors). None of these are able to simultaneously ameliorate acute dermatitis and mucositis, prevent the occurrence of fibrosis, and reduce late tumorigenesis; moreover, toxicities, side effects, tumor protection possibilities, and a lack of antitumor effects are troublesome.